Researchers Cut Gene Estimate

Kristen Philipkoski
02.12.01

Two papers to be published Monday in the world's most prestigious scientific journals claim that humans have about 30,000 genes, barely a third of the number first estimated. But some researchers dispute these findings and stick with the original estimates.

Eight months ago, rival groups of scientists, one a for-profit company and one a publicly funded international consortium, announced they had a working draft of a human genome map.

Now, both groups are publishing monumental papers describing how they did it in rival journals, Science and Nature. The scientists have partially deciphered what the genome map tells us and are using the papers to show the research community how they spent the last decade -- and about $3 billion.

"Breathtaking would be a word that comes to mind," said George Weinstock, co-director of the Baylor College of Medicine genome sequencing center, which contributed to the publically financed Human Genome Project. "This is the meat."

But the more scientists learn about the human genome, the more confounding the hereditary makeup of a human being seems to be.

Not only did the researchers find that the number of genes is much lower than previously thought, but the number of unique genes a human has that a mouse doesn't is estimated to be only about 300.

We have only twice the number of genes as the fruit fly, and about the same amount as an ear of corn.

"If you get upset about having only twice the amount of DNA as the fruit fly, think of that the next time your eating an ear of corn," Venter said.

Scientists now face the challenge of understanding what makes humans so much more complex than other species.

"If anyone found the basis for the pride of our species in the number of genes we had, they may have to rethink it," said Craig Venter, president and chief scientific officer of Celera Genomics, (CRA) the for-profit company.

Researchers believe that in fact proteins are much more responsible for creating human complexity than genes. For years, proteins have been called the workhorses of the human body, and the moniker seems even more fitting now.

"The 30,000 genes can actually generate many more, perhaps hundreds of thousands of proteins," said John McPherson, co-director of the genome sequencing center at Washington University in St. Louis.

After a gene makes a protein, it can be modified even more by other biological influences, creating even more complexity.

"This shows how irrelevant human gene patents are," Venter said. "The drug industry has been saying 'one gene, one patent, one drug'. But the uses for this approach can be counted on fingers."

That's surely a disconcerting assertion for companies like Human Genome Sciences (HGSI) and Incyte Genomics (INCY), which have spent the last several years stockpiling gene patents, hoping that one day they would lead to drugs.

Bill Haseltine, president of Human Genome Sciences, said that he believes both papers are wrong. He maintains that there are 120,000 genes, which he said is a more accurate figure than either the Celera or Human Genome Project estimates.

"If two independent groups arrive at the same answer and say it's right, that isn't always true," he said. "I was taught that the human being had 48 chromosomes -- it was in all textbooks. Now we know there are 46. That's the kind of mistake that can be institutionalized."

But researchers at Celera, which is publishing its findings in Science, and the Human Genome Project, which will report results in Nature, feel strongly that they are correct.

"Given all the tools that we threw at this problem, we cannot imagine that there are many more genes," said Mark Adams, vice president at Celera.

Randy Scott, the chairman of the board of Incyte Genomics, said he wasn't alarmed by the small number of genes.

"It makes life a lot more interesting because a certain amount of narrowing down means understanding which genes are involved in which diseases gets a little simpler," Scott said.

Incyte holds thousands of patents on genes, and Scott said now its portfolio looks even stronger. He also said that Incyte will take its cue from the publications and focus on proteins as well as genes.

"We want to understand biology and all its complexity," he said.

Researchers even have a running bet over how many human genes there really are. Wagers began at a genome sequencing meeting at Cold Spring Harbor Laboratories last April.

The winner will be announced at the 2003 Cold Spring Harbor Meeting, the 50th anniversary of the discovery of the structure of DNA.

Dr. James Watson, who was one of the scientists who discovered the DNA structure in 1953, recently said that 30,000 genes actually isn't really such a small number.

"Imagine a play with 3,000 actors," he said. "Youd tend to get confused."